Antigen (Ag) assays are of increasing importance as diagnostic tools, e.g., for the diagnosis of infectious diseases in humans or animals. In addition, quantitative measurement of Ag is useful for the follow-up of infected individuals. In viral infections, for example, the determination of the viral load is important with respect to prognosis, indication for antiviral treatment, or assessment of treatment success. Unfortunately, in the presence of antibody (Ab) the Ag becomes bound in immune complexes (IC). Such complexed Ag is no longer freely available to binding to the immune reagents used in antigen assays, i.e., detection by such assays, as demonstrated in the case of infection with the human immunodeficiency virus, HIV (de Wolf et al., Br. Med. J., 295:569-572, 1987; Pedersen et al., Br. Med. J., 295:567-569, 1987; Lange et al., AIDS, 1:15-20, 1987). Several groups have developed IC dissociation procedures based on either treatment with acids (for an example see Lange et al., AIDS, 1:15-20, 1987) or bases. While these procedures lead to a significantly higher detection rate of antigenemia (Nishanian et al., J. Inf. Dis., 162:21-28, 1990; Miles et al., N. Engl. J. Med., 328:297-302 1992), convincing data showing that they are capable of freeing all IC-bound Ag, thus making possible a truly quantitative measurement, have not been presented.
Another problem that impairs the quality of Ag assays is the presence of rheumatoid factors (RF) in a test sample, i.e., of antibodies that have specificity for immunoglobulins. Such rheumatoid factors may link the capture and tracer antibodies used in an Ag assay, thereby leading to overestimation of Ag concentrations or outright false-positive results. The usual way to deal with rheumatoid factors is their preabsorption with high concentrations of immunoglobulin. However, this does not represent a safe remedy, and its effect cannot be readily controlled.